Serious injury of the cervical and upper thoracic spinal cord results in serious cardiovascular dysfunction. Chief among these dysfunctions are the inability to achieve an upright posture without fainting (orthostatic hypotension) and large increases in arterial pressure (potentially leading to stroke) precipitated by sensory input to the spinal cord below the injury (hypertensive crises). Orthostatic hypotension is caused largely by the loss of descending control of the sympathetic component of baroreceptor regulation. Hypertensive crises are exacerbated by the same loss. Therefore, restoration of baroreceptor regulation of arterial pressure is important to recovery of cardiovascular control after spinal cord injury. Recently, we observed that rats spontaneously recover some degree of baroreceptor function, even after incomplete, but severe, spinal cord injury. Because few spinal cord injuries are complete transections, this discovery suggests that, if we understood the mechanism(s) for recovery, we could design treatments that would accelerate or improve it. In Aim 1, we will study the relationship between the site of spinal cord lesions and the degree of recovery of baroreceptor regulation. These experiments will indicate the most likely spinal or brainstem region(s) responsible for recovery. They will also determine the time-course of recovery, which will aid in planning the experiments of Aims 2 and 3. Aim 2 will use state-of-the-art neuroanatomical methods to characterize the structural changes that mediate recovery. This Aim will test directly our hypothesis that recovery is due to the formation of new synapses between intact (uninjured) descending pathways and propriospinal connections to sympathetic preganglionic neurons. In Aim 3, we will use growth factors to facilitate recovery of baroreceptor regulation. Treatment timing and treatment regions will be determined by the results of Aims 1 and 2. Because administration of growth factors may lead to untoward side effects, not only the efficacy, but the safety, of these treatments will be assessed. PUBLIC HEALTH RELEVANCE: People who have injured their spinal cords seriously usually have difficulty controlling their blood pressure. Yet, some animals, including people, slowly regain some control of their blood pressure over time. The purpose of our research is to understand how this recovery takes place and to develop methods for promoting recovery.